Asymmetric syntheses of two of GlaxoSmithKline’s highly potent phosphodiesterase IV inhibitors CMPI 1 and CMPO 2 have been accomplished from nitroethane and simple precursors in 8 and 7 steps, respectively. The suggested synthetic strategy involves as a key stage the silylation of enantiopure six-membered cyclic nitronates. In vitro studies of PDE IVB1 inhibition revealed a significant difference in the activity of CMPI 1 and CMPO 2 enantiomers.
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